Original article| Volume 60, ISSUE 12, P1309-1313, December 15, 2006

Serum Free Fatty Acids and Glucose Metabolism, Insulin Resistance in Schizophrenia with Chronic Antipsychotics


      Weight gain and type 2 diabetes mellitus (DM) are often linked to antipsychotics treatment. The aim of the study is to investigate serum free fatty acids (FFA) levels in schizophrenic patients who received long-term antipsychotics treatment, and to explore the associations between serum FFA and fasting blood glucose, and insulin resistance.


      308 inpatients with schizophrenia who met with the criteria of DSM-IV were recruited into this study, and were divided into four groups: control subjects, single obesity, impaired glucose tolerance (IGT) and type 2 DM according to different body mass index, fasting blood glucose level and 2-hour postprandial blood glucose. Serum FFA was measured with colorimetry. Serum insulin and leptin were measured with radioimmunoassay respectively.


      There was a significant elevation in serum FFA levels in schizophrenic patients who received long-term antipsychotics treatment, especially in single obesity, IGT, and DM groups. The elevated serum FFA was remarkably positive correlated with fasting blood glucose and insulin resistance.


      The study suggested the elevated serum FFA in schizophrenic patients with long-term antipsychotics treatment affected the blood glucose metabolism, may have played an important role in insulin resistance and type 2 DM, and was also an important trait of metabolic syndromes.

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        • Anuurad E.
        • Shiwaka K.
        • Nogi A.
        • Kitajima K.
        • Enkhmaa B.
        • Shimono K.
        • et al.
        The new BMI criteria for Asians by the regional office for the western pacific region of WHO are suitable for screening of overweight to prevent metabolic syndrome in elder Japanese workers.
        J Occup Health. 2003; 45: 335-343
        • Buse J.B.
        Metabolic side effects of antipsychotics: focus on hyperglycemia and diabetes.
        J Clin Psychiatry. 2002; 63: 37-41
        • Carpentier A.
        • Mittelman S.D.
        • Lamarche B.
        • Bergman R.N.
        • Giacca A.
        • Lewis G.F.
        • et al.
        Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation.
        Am J Physiol. 1999; 276: E1055-E1066
        • Chu C.A.
        • Sherck S.M.
        • Igawa K.
        Effects of free fatty acids on heptic glycogenolysis and gluconeo-genesis in conscious dogs.
        Am J Psyiol Endocrinal Metab. 2002; 282: E402-E411
        • Dhindsa S.
        • Tripathy D.
        • Sanalkumar N.
        • Ravishankar S.
        • Ghanim H.
        • Aljada A.
        • et al.
        Free fatty acid induced insulin resistance in the obese is not prevented by rosiglitazone treatment.
        J Clin Endocrinol Metab. 2005; 90: 5058-5063
        • Dresner A.
        • Laurent D.
        • Marcucci M.
        • Griffin M.E.
        • Dufour S.
        • Cline G.W.
        • et al.
        Effects of free fatty acids on glucose transport and IRS-1- associated phosphatidylinositol 3-kinase activity.
        J Clin Invest. 1999; 103: 253-259
        • Hägg S.
        • Joelsson L.
        • MjÖrndal T.
        • Spigset O.
        • Oja G.
        • Dahlqvist R.
        Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications.
        J Clin Psychiatry. 1998; 59: 294-299
        • Hawkins M.
        • Tonelli J.
        • Kishore P.
        Contribution of elevated free acid levels to the lack of glucose effectives in type 2 diabetes.
        Diabetes. 2003; 52: 2748-2758
        • Heiskanen T.
        • Niskanen L.
        • Lyytikäinen R.
        • Saarinen P.I.
        • Hintikka J.
        Metabolic syndrome in patients with schizophrenia.
        J Clin Psychiatry. 2003; 64: 575-579
        • Henderson D.C.
        • Cagliero E.
        • Copeland P.M.
        • Borba C.P.
        • Evins E.
        • Hayden D.
        • et al.
        Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents.
        Arch Gen Psychiatry. 2005; 62: 19-28
        • Henderson D.C.
        Atypical antipsychotic-induced diabetes mellitus: how strong is the evidence?.
        CNS Drugs. 2002; 16: 77-89
        • Hennes M.M.
        • Dua A.
        • Kissebah A.H.
        Effects of free fatty acids and glucose on splanchnic insulin dynamics.
        Diabetes. 1997; 46: 57-62
        • Hermans M.P.
        • Levy J.C.
        • Morris R.J.
        • Turner R.C.
        Comparison of insulin sensitivity tests across a range of glucose tolerance from normal to diabetes.
        Diabetologia. 1999; 42: 678-687
        • Lebovitz H.E.
        Diagnosis, classification, and pathogenesis of diabetes mellitus.
        J Clin Psychiatry. 2001; 62: 5-9
        • Lieberman J.A.
        • Tollefson G.
        • Tohen M.
        • Green A.I.
        • Gur R.E.
        • Kahn R.
        • et al.
        Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: A randomized, double-blinded trial of olanzapine versus haloperidol.
        Am J Psychiatry. 2003; 160: 1401-1403
        • Lupi R.
        • Dotta F.
        • Marselli L.
        • Guerra S.D.
        • Masini M.
        • Santangelo C.
        • et al.
        Prolonged Exposure to Free Fatty Acids has Cytostatic and Pro-Apoptotic Effects on Human Pancreatic Islets.
        Diabetes. 2002; 51: 1437-1442
        • Matsuoka N.
        • Ogawa Y.
        • Hosoda K.
        • Matsuda J.
        • Masuzaki H.
        • Miyawaki T.
        Human leptin receptor gene in obese japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity.
        Diabetologia. 1997; 40: 1204-1210
        • Mukherjee S.
        • Decina P.
        • Bocola V.
        • Saraceni F.
        • Scapicchio P.L.
        Diabetes mellitus in schizophrenic patients.
        Compr Psychiatry. 1996; 37: 68-73
        • Newcomer J.W.
        Metabolic disturbances associated with antipsychotic use.
        J Clin Psychiatry. 2001; 62: 3
        • Perez-Martin A.
        • Raynaud E.
        • Hentgen C.
        • Bringer J.
        • Mercier J.
        • Brun J.F.
        • et al.
        Simplified measurement of insulin sensitivity with the mininmal model procedure in type 2 diabetic patients without measurement of insulinemia.
        Horm Metab Res. 2002; 34: 102-106
        • Seufert J.
        Leptin effects on pancreatic β-cell gene expression and function.
        Diabetes. 2004; 53: S152-S158
        • Shulman G.I.
        Cellular mechanisms of insulin resistance.
        J Clin Invest. 2000; 106: 171-176
        • Stromblad G.
        • Bjorntorp P.
        Reduced hepatic insulin clearance in rats with dietary-induced obesity.
        Metabolism. 1986; 35: 323-327
        • Tremblay F.
        • Lavigne C.
        • Jacques H.
        • Marette A.
        Defective insulin-induced GLUT4 translocation in skeletal muscle of high fat-fed rats is associated with alternation in both Akt/protein kinase B and atypical protein kinase C (zeta/lambda) activities.
        Diabetes. 2001; 50: 1901-1910